The popularity and efficacy of Glucagon-like Peptide-1 Receptor Agonists, GLP-1’S, have been overwhelming the last 3-5 years. I’ve written about various aspects of these drugs on several occasions because they have absolutely revolutionized the topic of weight loss. Two of these drugs, semaglutide (Ozempic, Wegovy) and tirzepatide (Zepbound, Mounjaro), have stood out as more effective for weight loss and have captured the bulk of the market. Weight loss averages with Tirzepatide exceed those of semaglutide by 5%, or roughly 10 lbs.
I have been on tirzepatide for almost five months and have dropped from 280lbs to 248lbs, or 32 lbs. Last month I wrote about my experience with Zepbound which seems to coincide with what others have experienced, as well.
One of the major problems with losing weight while on a GLP-1’s is not during the weight loss phase, but instead after you reach your goal weight. If you abruptly stop taking tirzepatide, your appetite returns, and you regain weight. How much you regain depends on how deeply you fall into you old eating habits and negative lifestyle. People have been known to re-gain 20+ pounds in a matter of a few weeks.
Doctors at the Mayo Clinic in Rochester, Minnesota, have researched this concern and have come up with three options that will prevent patients from regaining weight after achieving their goal weight. These three options are:
1. Dose de-escalation
2. Interval dosing
3. Add-on strategy
Dose de-escalation: Patients taper off the medication gradually to “mitigate,” or alleviate, the risk of increasing appetite and eating too much, or the wrong foods. It may require 20 weeks of tapering to prevent weight re-gain.
Interval Dosing: the interval between injections is gradually lengthened. Normal dosing is every 7 days. Start by taking the drug every 10 days for awhile, then every 15 days, working gradually up to every 21 days. These drugs have a long half-life so they will maintain sufficient appetite suppression to remain at a stable weight or lose weight again.
Add-on: Try adding an older drug (eg. phentermine-topiramate) to the GLP-1, or alone. These drugs are still marketed and still have the ability to cause weight loss. Maintaining lifestyle changes is very important.
If you find yourself unable to afford a GLP-1, or if adverse effects are becoming a problem, and you can no longer take it, you now have three alternative choices to keep from regaining the weight you suffered a lot to lose.
I imagine, one day, GLP-1 researchers will come up with a new and improved GLP-1 that will somehow have more lasting, long term effects and can be taken infrequently or not at all.
Reference: Rajjo T, Bechenati D, Hoyas D, Shah M. Long-term use of Obesity Management Medications: Challenges and Discontinuation Strategies. Am Fam Phys 2026 Feb;113(2):118-119.
